TY - JOUR
T1 - Inhibiting CDK in Cancer Therapy
T2 - Current Evidence and Future Directions
AU - Vijayaraghavan, Smruthi
AU - Moulder, Stacy
AU - Keyomarsi, Khandan
AU - Layman, Rachel M.
N1 - Publisher Copyright:
© 2017, Springer International Publishing AG, part of Springer Nature.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Cell cycle dysregulation is a hallmark of all cancers, resulting in uncontrolled proliferation. Cyclin dependent kinases (CDKs), a family of proteins that are involved in the regulation of the cell cycle, are frequently overexpressed or mutated in cancer. Hence, CDK-inhibiting drugs have been developed and evaluated as cancer therapeutics. Clinical trials have shown CDK4/6 inhibitors (CDK4/6i) to be relatively safe and effective, and these are now standard of care treatment for advanced hormone receptor positive breast cancer. Some CDK4/6i drugs are also able to cross the blood brain barrier and may, therefore, offer effective therapy for primary and metastatic central nervous system malignancies. Ongoing research is also evaluating CDK4/6i for additional breast cancer subtypes and non-breast malignancies with promising early phase clinical trial results. Finally, pre-clinical research has identified potential biomarkers for CDK4/6i efficacy and is exploring potential resistance mechanisms to this treatment. Further clinical-translational research is needed to advance patient selection and combinatorial treatment strategies with CDK4/6i in breast cancer and other malignancies.
AB - Cell cycle dysregulation is a hallmark of all cancers, resulting in uncontrolled proliferation. Cyclin dependent kinases (CDKs), a family of proteins that are involved in the regulation of the cell cycle, are frequently overexpressed or mutated in cancer. Hence, CDK-inhibiting drugs have been developed and evaluated as cancer therapeutics. Clinical trials have shown CDK4/6 inhibitors (CDK4/6i) to be relatively safe and effective, and these are now standard of care treatment for advanced hormone receptor positive breast cancer. Some CDK4/6i drugs are also able to cross the blood brain barrier and may, therefore, offer effective therapy for primary and metastatic central nervous system malignancies. Ongoing research is also evaluating CDK4/6i for additional breast cancer subtypes and non-breast malignancies with promising early phase clinical trial results. Finally, pre-clinical research has identified potential biomarkers for CDK4/6i efficacy and is exploring potential resistance mechanisms to this treatment. Further clinical-translational research is needed to advance patient selection and combinatorial treatment strategies with CDK4/6i in breast cancer and other malignancies.
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U2 - 10.1007/s11523-017-0541-2
DO - 10.1007/s11523-017-0541-2
M3 - Review article
C2 - 29218622
AN - SCOPUS:85037331636
SN - 1776-2596
VL - 13
SP - 21
EP - 38
JO - Targeted oncology
JF - Targeted oncology
IS - 1
ER -